Selenium and Diabetes: More Bad News for Supplements

In this issue, Stranges and colleagues (1) report findings from the NPC (Nutritional Prevention of Cancer) trial that show an increased risk for diabetes among participants randomly assigned to receive supplements with 200 μg of selenium daily for 7.7 years compared with placebo. This effect was largely limited to participants in the top tertile of plasma selenium levels at baseline (>121.6 ng/mL). In this group, the hazard ratio for incident diabetes in persons using selenium supplements compared with placebo was 2.70 (95% CI, 1.30 to 5.61). The NPC trial is the largest and longest available experimental study of selenium supplements compared with placebo. Although diabetes was not a primary end point of the trial and the investigators used self-report and medical records to assign the diagnosis, the results have credibility because of the randomized, double-blind design; the monitoring of baseline and follow-up plasma selenium levels; and other methodological strengths. The public health implications of these findings are substantial: More than 1% of the U.S. population take selenium supplements, and more than 35% take multivitamin and multimineral supplements (2) that often contain selenium.

Before it was found to be an essential nutrient (3, 4), selenium was considered highly toxic to animals and humans (5). The key breakthrough occurred in 1973, when Rotruck and colleagues (3) discovered that selenium protected against oxidative damage by means of selenium-dependent glutathione peroxidase. Selenium is incorporated into selenoproteins as selenocysteine through a complex genetic mechanism encoded by the UGA codon (6). Selenoproteins, including glutathione peroxidases, thioredoxin reductases, iodothyronine deiodinases, and selenoprotein P, have important enzymatic functions. Through selenoproteins, selenium is involved in many biological …